Taxanes such as paclitaxel and docetaxel are considered as important anticancer drugs. They are mitotic inhibitors used in cancer chemotherapy, which act by interfering in the normal microtubule growth during cell division. They bind to β-tubulin subunits of microtubules, preventing depolymerization of the mitotic spindle, thereby leading to cell cycle arrest, inhibits cell replication and eventually promoting apoptosis. Paclitaxel has displayed significant antitumor activity against non-small-cell lung cancer (NSCLC), ovarian, head and neck tumors and breast cancer as well as in preventing restenosis. Despite the excellent antitumor properties of these drugs, paclitaxel, as well as the other closely related compounds suffer from significant disadvantages among which is low water solubility, certain toxic effects (myelosuppression, neutropenia, hypersensitivity reactions and fluid retention). Such side effects limit the clinically administrable dose.
Matrix metalloproteinases (MMPs) are enzymes that regulate cell-matrix composition. They are involved in normal and pathological process, including cancer, inflammation, arthritis, cardiovascular diseases and others. Cancer growth and dissemination involve multiple Matrix metalloproteinases that direct the interactions of tumor cells with the surrounding matrix. Indeed, inhibition of metalloproteinases reduces the malignant potential of experimental tumors. MMP-2 (Matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase)) has attracted attention since it was found as a key component of cancer cell migration across collagen by a mechanism involving CBD-mediated MMP-2 interactions with collagen. Thus, it is associated with is tumor invasion and formation of metastases. Metastasis is defined as spread of cancer through the bloodstream and lymphatic system to other parts of the body where they form metastases. Lipoic acid is a chiral compound consisting of a carboxylic acid and a cyclic disulfide. It is an essential factor for aerobic life and a common dietary supplement. It is an antioxidant needed for the activity of enzyme complexes such as those of pyruvate dehydrogenase and glycine decarboxylase. In its reduced form (Dihydrolipoic acid) it influences a number of cell processes by direct radical scavenging, recycling of other antioxidants, increasing glutathione synthesis and modulating transcription factor activity.